PMID- 31023003 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220409 IS - 2005-3606 (Print) IS - 2005-5447 (Electronic) IS - 2005-3606 (Linking) VI - 12 IP - 2 DP - 2019 Jul 31 TI - Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Umbilical Cord-Derived Mesenchymal Stem Cells. PG - 291-303 LID - 10.15283/ijsc19002 [doi] AB - BACKGROUND AND OBJECTIVES: There have been contradictory reports on the pro-cancer or anti-cancer effects of mesenchymal stem cells. In this study, we investigated whether conditioned medium (CM) from hypoxic human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) (H-CM) showed enhanced anti-cancer effects compared with CM from normoxic hUC-MSCs (N-CM). METHODS AND RESULTS: Compared with N-CM, H-CM not only strongly reduced cell viability and increased apoptosis of human cervical cancer cells (HeLa cells), but also increased caspase-3/7 activity, decreased mitochondrial membrane potential (MMP), and induced cell cycle arrest. In contrast, cell viability, apoptosis, MMP, and cell cycle of human dermal fibroblast (hDFs) were not significantly changed by either CM whereas caspase-3/7 activity was decreased by H-CM. Protein antibody array showed that activin A, Beta IG-H3, TIMP-2, RET, and IGFBP-3 were upregulated in H-CM compared with N-CM. Intracellular proteins that were upregulated by H-CM in HeLa cells were represented by apoptosis and cell cycle arrest terms of biological processes of Gene Ontology (GO), and by cell cycle of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In hDFs, negative regulation of apoptosis in biological process of GO and PI3K-Akt signaling pathway of KEGG pathways were represented. CONCLUSIONS: H-CM showed enhanced anti-cancer effects on HeLa cells but did not influence cell viability or apoptosis of hDFs and these different effects were supported by profiling of secretory proteins in both kinds of CM and intracellular signaling of HeLa cells and hDFs. FAU - Han, Kyu-Hyun AU - Han KH AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Kim, Ae-Kyeong AU - Kim AK AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Jeong, Gun-Jae AU - Jeong GJ AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Jeon, Hye Ran AU - Jeon HR AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Bhang, Suk Ho AU - Bhang SH AD - Sungkyunkwan University School of Chemical Engineering, Suwon, Korea. FAU - Kim, Dong-Ik AU - Kim DI AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. LA - eng PT - Journal Article PL - Korea (South) TA - Int J Stem Cells JT - International journal of stem cells JID - 101497587 PMC - PMC6657944 OTO - NOTNLM OT - Anti-cancer OT - Conditioned medium OT - Fibroblasts OT - Hypoxia OT - Mesenchymal stem cells COIS- Potential Conflict of Interest The authors have no conflicting financial interest. EDAT- 2019/04/27 06:00 MHDA- 2019/04/27 06:01 PMCR- 2019/04/30 CRDT- 2019/04/27 06:00 PHST- 2019/01/02 00:00 [received] PHST- 2019/03/05 00:00 [revised] PHST- 2019/03/06 00:00 [accepted] PHST- 2019/04/27 06:00 [pubmed] PHST- 2019/04/27 06:01 [medline] PHST- 2019/04/27 06:00 [entrez] PHST- 2019/04/30 00:00 [pmc-release] AID - ijsc19002 [pii] AID - ijsc-12-291 [pii] AID - 10.15283/ijsc19002 [doi] PST - ppublish SO - Int J Stem Cells. 2019 Jul 31;12(2):291-303. doi: 10.15283/ijsc19002.